tbuckley/cabot-search huggingface dataset:
Predictive Value of Minimal Residual Disease for Efficacy of Rituximab Maintenance in Mantle Cell Lymphoma: Results From the European Mantle Cell Lymphoma Elderly Trial
Authors: Eva Hoster, Marie-Hélène Delfau-Larue, Elizabeth Macintyre, Linmiao Jiang, Stephan Stilgenbauer, Ursula Vehling-Kaiser, Gilles Salles, Catherine Thieblemont, Hervé Tilly, Stefan Wirths, Pierre Feugier, Kai Hübel, Christian Schmidt, Vincent Ribrag, Johanna C. Kluin-Nelemans, Martin Dreyling, Christiane Pott
Journal: Journal of Clinical Oncology (2023)

PURPOSE The outcome of older patients with mantle cell lymphoma (MCL) has improved by the introduction of immunochemotherapy, followed by rituximab (R)-maintenance. Assessment of minimal residual disease (MRD) represents a promising tool for individualized treatment decisions and was a prospectively planned part of the European MCL Elderly trial. We investigated how MRD status influenced the efficacy of R-maintenance and how MRD can enable tailored consolidation strategies. PATIENTS AND METHODS Previously untreated patients with MCL age 60 years or older have been randomly assigned to R versus interferon-alpha maintenance after response to rituximab, fludarabine, cyclophosphamide (R-FC) versus rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). MRD monitoring was performed by real-time quantitative polymerase chain reaction (qPCR) following EuroMRD guidelines. RESULTS A qPCR assay with a median sensitivity of 1 × 10 −5 could be generated in 80% of 288 patients in an international, multicenter, multilaboratory setting. More extensive tumor dissemination facilitated the identification of a molecular marker. The efficacy of R-maintenance in clinical remission was confirmed for MRD-negative patients at the end of induction in terms of progression-free survival (PFS; hazard ratio [HR], 0.38 [95% CI, 0.21 to 0.63]) and overall survival (OS; HR, 0.37 [95% CI, 0.20 to 0.68]), particularly in R-CHOP–treated patients (PFS-HR, 0.23 [95% CI, 0.10 to 0.52]; OS-HR, 0.19 [95% CI, 0.07 to 0.52]). R-maintenance appeared less effective in MRD-positive patients (PFS-HR, 0.51 [95% CI, 0.26 to 1.02]) overall and after R-CHOP induction (PFS-HR, 0.59 [95% CI, 0.28 to 1.26]). R-FC achieved more frequent and faster MRD clearance compared with R-CHOP. MRD positivity in clinical remission after induction was associated with a short median time to clinical progression of approximately 1-1.7 years. CONCLUSION The results confirm the strong efficacy of R-maintenance in patients who are MRD-negative after induction. Treatment de-escalation for MRD-negative patients is discouraged by our results. More effective consolidation strategies should be explored in MRD-positive patients to improve their long-term prognosis.
Incarceration and screen-detectable cancer diagnosis among adults in Connecticut
Authors: Ilana B Richman, Pamela R Soulos, Hsiu-ju Lin, Jenerius A Aminawung, Oluwadamiloa T Oladeru, Lisa B Puglisi, Emily A Wang, Cary P Gross
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Although incarcerated adults are at elevated risk of dying from cancer, little is known about cancer screening in carceral settings. This study compared stage-specific incidence of screen-detectable cancers among incarcerated and recently released people with the general population, as a reflection of screening practices. We calculated the age- and sex-standardized incidence ratios (SIR) for early- and late-stage cancers for incarcerated and recently released adults compared to the general Connecticut population between 2005 and 2016. Our sample included 143 cancer cases among those incarcerated, 406 among those recently released, and 201 360 in the general population. The SIR for early-stage screen-detectable cancers was lower among incarcerated (SIR = 0.28, 95% CI = 0.17 to 0.43) and recently released (SIR = 0.69, 95% CI = 0.51 to 0.88) individuals than the general population. Incidence of late-stage screen-detectable cancer was lower during incarceration (SIR = 0.51, 95% CI = 0.27 to 0.88) but not after release (SIR = 1.32, 95% CI = 0.93 to 1.82). Findings suggest that underscreening and underdetection of cancer may occur in carceral settings.
Efficacy and safety of abrocitinib in patients with moderate‐to‐severe atopic dermatitis and comorbid allergies
Authors: Peter Schmid‐Grendelmeier, Melinda J. Gooderham, Karin Hartmann, George N. Konstantinou, Marc Fellmann, Christopher Koulias, Claire Clibborn, Pinaki Biswas, Patrick M. Brunner
Journal: Allergy (2023)

Abstract Background Abrocitinib efficacy by comorbidity status in patients with moderate‐to‐severe atopic dermatitis (AD) has not been previously assessed. This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with AD and allergic comorbidities. Methods Data were pooled from patients who received abrocitinib 200 mg, 100 mg, or placebo in phase 2b (NCT02780167) and phase 3 (NCT03349060, NCT03575871) monotherapy trials. Patients with and without allergic comorbidities (allergic asthma, rhinitis, conjunctivitis, or food allergy) were evaluated for Investigator's Global Assessment (IGA) response (clear [0] or almost clear [1]), ≥75% improvement in the Eczema Area and Severity Index (EASI‐75), ≥4‐point improvement in Peak Pruritus Numerical Rating Scale (PP‐NRS4), and Dermatology Life Quality Index (DLQI) response (&lt;2 with baseline score ≥2). Other outcomes were Patient‐Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD), and treatment‐emergent adverse events (TEAEs). Results Of 942 patients, 498 (53%) reported at least one allergic comorbidity (asthma only, 33%; conjunctivitis only or rhinitis only or both, 17%; food allergies only, 15%; &gt;1 allergic comorbidity, 34%). Regardless of comorbidity status, from Week 2 to Week 12, higher percentages of patients treated with either abrocitinib dose achieved IGA 0/1, EASI‐75, PP‐NRS4, or DLQI 0/1 versus placebo‐treated patients. Changes from baseline in POEM, SCORAD, and PSAAD were greater with abrocitinib than with placebo in patients with and without allergic comorbidities. Most TEAEs were mild or moderate. Conclusions Efficacy and safety data support abrocitinib use to manage AD in patients with or without allergic comorbidities.
Preclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency
Authors: Judith Y. Altarejos, Jeffrey Pangilinan, Simona Podgrabinska, Baris Akinci, Maria Foss-Freitas, Adam H. Neidert, Yonaton Ray, Wenjun Zheng, Steven Kim, Vishal Kamat, Meilin Huang, Soo Min, Jason Mastaitis, Giselle Dominguez-Gutierrez, Jee-Hae Kim, Panayiotis Stevis, Tammy Huang, Brian Zambrowicz, William C. Olson, Stephen Godin, Elizabeth Bradley, Andrew D. Gewitz, Mark Baker, Rita Hench, Matthew S. Davenport, Thomas L. Chenevert, Frank DiPaola, George D. Yancopoulos, Andrew J. Murphy, Gary A. Herman, Bret J. Musser, Hayes Dansky, Joyce Harp, Jesper Gromada, Mark W. Sleeman, Elif A. Oral, Benjamin A. Olenchock
Journal: Science Translational Medicine (2023)

Deficiency in the adipose-derived hormone leptin or leptin receptor signaling causes class 3 obesity in individuals with genetic loss-of-function mutations in leptin or its receptor LEPR and metabolic and liver disease in individuals with hypoleptinemia secondary to lipoatrophy such as in individuals with generalized lipodystrophy. Therapies that restore leptin-LEPR signaling may resolve these metabolic sequelae. We developed a fully human monoclonal antibody (mAb), REGN4461 (mibavademab), that activates the human LEPR in the absence or presence of leptin. In obese leptin knockout mice, REGN4461 normalized body weight, food intake, blood glucose, and insulin sensitivity. In a mouse model of generalized lipodystrophy, REGN4461 alleviated hyperphagia, hyperglycemia, insulin resistance, dyslipidemia, and hepatic steatosis. In a phase 1, randomized, double-blind, placebo-controlled two-part study, REGN4461 was well tolerated with an acceptable safety profile. Treatment of individuals with overweight or obesity with REGN4461 decreased body weight over 12 weeks in those with low circulating leptin concentrations (<8 ng/ml) but had no effect on body weight in individuals with higher baseline leptin. Furthermore, compassionate-use treatment of a single patient with atypical partial lipodystrophy and a history of undetectable leptin concentrations associated with neutralizing antibodies to metreleptin was associated with noteable improvements in circulating triglycerides and hepatic steatosis. Collectively, these translational data unveil an agonist LEPR mAb that may provide clinical benefit in disorders associated with relatively low leptin concentrations.
Obesity and lifespan, a complex tango
Authors: Alberto Diaz-Ruiz, Nathan L. Price, Luigi Ferrucci, Rafael de Cabo
Journal: Science Translational Medicine (2023)

Obesity and aging share comorbidities, phenotypes, and deleterious effects on health that are associated with chronic diseases. However, distinct features set them apart, with underlying biology that should be explored and exploited, especially given the demographic shifts and the obesity epidemic that the world is facing.
Evidence for the contribution of the gut microbiome to obesity and its reversal
Authors: Douwe F. de Wit, Nordin M. J. Hanssen, Koen Wortelboer, Hilde Herrema, Elena Rampanelli, Max Nieuwdorp
Journal: Science Translational Medicine (2023)

Obesity has become a worldwide pandemic affecting more than 650 million people and is associated with a high burden of morbidity. Alongside traditional risk factors for obesity, the gut microbiome has been identified as a potential factor in weight regulation. Although rodent studies suggest a link between the gut microbiome and body weight, human evidence for causality remains scarce. In this Review, we postulate that existing evidence remains to establish a contribution of the gut microbiome to the development of obesity in humans but that modified probiotic strains and supraphysiological dosages of microbial metabolites may be beneficial in combatting obesity.
Metaflammation in obesity and its therapeutic targeting
Authors: Michael W. Schleh, Heather L. Caslin, Jamie N. Garcia, Mona Mashayekhi, Gitanjali Srivastava, Anna B. Bradley, Alyssa H. Hasty
Journal: Science Translational Medicine (2023)

Obesity-associated inflammation is a systemic process that affects all metabolic organs. Prominent among these is adipose tissue, where cells of the innate and adaptive immune system are markedly changed in obesity, implicating these cells in a range of processes linking immune memory to metabolic regulation. Furthermore, weight loss and weight cycling have unexpected effects on adipose tissue immune populations. Here, we review the current literature on the roles of various immune cells in lean and obese adipose tissue. Within this context, we discuss pharmacological and nonpharmacological approaches to obesity treatment and their impact on systemic inflammation.
Hyperleptinemia contributes to antipsychotic drug–associated obesity and metabolic disorders
Authors: Shangang Zhao, Qian Lin, Wei Xiong, Li Li, Leon Straub, Dinghong Zhang, Rizaldy Zapata, Qingzhang Zhu, Xue-Nan Sun, Zhuzhen Zhang, Jan-Bernd Funcke, Chao Li, Shiuhwei Chen, Yi Zhu, Nisi Jiang, Guannan Li, Ziying Xu, Steven C. Wyler, May-Yun Wang, Juli Bai, Xianlin Han, Christine M. Kusminski, Ningyan Zhang, Zhiqiang An, Joel K. Elmquist, Olivia Osborn, Chen Liu, Philipp E. Scherer
Journal: Science Translational Medicine (2023)

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug–induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly to the development of obesity and associated metabolic disorders. By suppressing the rise in leptin through the use of a monoclonal leptin-neutralizing antibody, we effectively prevented weight gain, restored glucose tolerance, and preserved adipose tissue and liver function in antipsychotic drug–treated mice. Mechanistically, suppressing excess leptin resolved local tissue and systemic inflammation typically associated with antipsychotic drug treatment. We conclude that hyperleptinemia is a key contributor to antipsychotic drug–associated weight gain and metabolic deterioration. Leptin suppression may be an effective approach to reducing the undesirable side effects of antipsychotic drugs.
Skeletal Muscle Involvement in Patients With Truncations of Titin and Familial Dilated Cardiomyopathy
Authors: Sofie Vinther Skriver, Bjørg Krett, Nanna Scharf Poulsen, Thomas Krag, Helle Rudkjær Walas, Alex Hørby Christensen, Henning Bundgaard, John Vissing, Christoffer Rasmus Vissing
Journal: JACC Heart Failure (2023)
Right Ventricle Pulmonary Artery Coupling and Renal Function in Patients With Severe Aortic Stenosis Undergoing TAVR
Authors: Simone Fezzi, Paolo Alberto Del Sole, Michele Pighi, Massimo Flaim, Concetta Mammone, Francesca Rizzetto, Domenico Tavella, Angela Mcinerney, Gabriele Pesarini, Giovanni Benfari, Roberto Scarsini, Darren Mylotte, Flavio Luciano Ribichini
Journal: JACC. Cardiovascular imaging (2023)
Interphylum dissemination of NDM-5-positive plasmids in hospital wastewater from Fuzhou, China: a single-centre, culture-independent, plasmid transmission study
Authors: Qiu E Yang, Xiaodan Ma, Lingshuang Zeng, Qinqin Wang, Minchun Li, Lin Teng, Mingzhen He, Chen Liu, Mengshi Zhao, Mengzhu Wang, Deng Hui, Jonas Stenløkke Madsen, Hanpeng Liao, Timothy R Walsh, Shungui Zhou
Journal: The Lancet Microbe (2023)

The global spread of plasmid-borne carbapenem resistance is an ongoing public health challenge; however, the nature of such horizontal gene transfer events among complex bacterial communities remains poorly understood. We examined the in-situ transfer of the globally dominant New Delhi metallo-β-lactamase (NDM)-5-positive IncX3 plasmid (denoted pX3_NDM-5) in hospital wastewater to simulate a real-world, One Health antimicrobial resistance context.
Operational greenhouse-gas emissions of deep learning in digital pathology: a modelling study
Authors: Alireza Vafaei Sadr, Roman Bülow, Saskia von Stillfried, Nikolas E J Schmitz, Pourya Pilva, David L Hölscher, Peiman Pilehchi Ha, Marcel Schweiker, Peter Boor
Journal: The Lancet Digital Health (2023)

Deep learning is a promising way to improve health care. Image-processing medical disciplines, such as pathology, are expected to be transformed by deep learning. The first clinically applicable deep-learning diagnostic support tools are already available in cancer pathology, and their number is increasing. However, data on the environmental sustainability of these tools are scarce. We aimed to conduct an environmental-sustainability analysis of a theoretical implementation of deep learning in patient-care pathology.
Neutrophil extracellular traps promote ΔNp63+ basal cell hyperplasia in chronic rhinosinusitis
Authors: Suha Lim, Roza Khalmuratova, Yun Young Lee, Yi Sook Kim, Mingyu Lee, Na Kyeong Lee, Se-Na Kim, Young Bin Choy, Chun Gwon Park, Dae Woo Kim, Hyun-Woo Shin
Journal: Journal of Allergy and Clinical Immunology (2023)
Compared to histamine-2 receptor antagonist, proton pump inhibitor induces stronger oral-to-gut microbial transmission and gut microbiome alterations: a randomised controlled trial
Authors: Jiaying Zhu, Chuqing Sun, Min Li, Guoru Hu, Xing-Ming Zhao, Wei-Hua Chen
Journal: Gut (2023)

Objective We aim to compare the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the gut microbiota through longitudinal analysis. Design Healthy volunteers were randomly assigned to receive either PPI (n=23) or H2RA (n=26) daily for seven consecutive days. We collected oral (saliva) and faecal samples before and after the intervention for metagenomic next-generation sequencing. We analysed intervention-induced alterations in the oral and gut microbiome including microbial abundance and growth rates, oral-to-gut transmissions, and compared differences between the PPI and H2RA groups. Results Both interventions disrupted the gut microbiota, with PPIs demonstrating more pronounced effects. PPI usage led to a significantly higher extent of oral-to-gut transmission and promoted the growth of specific oral microbes in the gut. This led to a significant increase in both the number and total abundance of oral species present in the gut, including the identification of known disease-associated species like Fusobacterium nucleatum and Streptococcus anginosus . Overall, gut microbiome-based machine learning classifiers could accurately distinguish PPI from non-PPI users, achieving an area under the receiver operating characteristic curve (AUROC) of 0.924, in contrast to an AUROC of 0.509 for H2RA versus non-H2RA users. Conclusion Our study provides evidence that PPIs have a greater impact on the gut microbiome and oral-to-gut transmission than H2RAs, shedding light on the mechanism underlying the higher risk of certain diseases associated with prolonged PPI use. Trial registration number ChiCTR2300072310.
2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases
Authors: Emma Dures, Bayram Farisoğulları, Eduardo José Ferreira Santos, Anna Molto, Caroline Feldthusen, Claire Harris, Corinna Elling-Audersch, Deirdre Connolly, Elena Elefante, Fernando Estévez-López, Ilaria Bini, Jette Primdahl, Kirsten Hoeper, Marie Urban, Mart A F J van de Laar, Marta Redondo, Peter Böhm, Raj Amarnani, Rhys Hayward, Rinie Geenen, Simona Rednic, Susanne Pettersson, Tanja Thomsen, Till Uhlig, Valentin Ritschl, Pedro M Machado
Journal: Annals of the Rheumatic Diseases (2023)

Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs.
Our Scientific Journey through the Ups and Downs of Blood Glucose Control in the ICU
Authors: Greet Van den Berghe, Ilse Vanhorebeek, Lies Langouche, Jan Gunst
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

This article tells the story of our long search for the answer to one question: Is stress hyperglycemia in critically ill patients adaptive or maladaptive? Our earlier work had suggested the lack of hepatic insulin effect and hyperglycemia as jointly predicting poor outcome. Therefore, we hypothesized that insulin infusion to reach normoglycemia, tight glucose control, improves outcome. In three randomized controlled trials (RCTs), we found morbidity and mortality benefit with tight glucose control. Moving from the bed to the bench, we attributed benefits to the prevention of glucose toxicity in cells taking up glucose in an insulin-independent, glucose concentration gradient-dependent manner, counteracted rather than synergized by insulin. Several subsequent RCTs did not confirm benefit, and the large Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation, or "NICE-SUGAR," trial found increased mortality with tight glucose control associated with severe hypoglycemia. Our subsequent clinical and mechanistic research revealed that early use of parenteral nutrition, the context of our initial RCTs, had been a confounder. Early parenteral nutrition (early-PN) aggravated hyperglycemia, suppressed vital cell damage removal, and hampered recovery. Therefore, in our next and largest "TGC-fast" RCT, we retested our hypothesis, without the use of early-PN and with a computer algorithm for tight glucose control that avoided severe hypoglycemia. In this trial, tight glucose control prevented kidney and liver damage, though with much smaller effect sizes than in our initial RCTs without affecting mortality. Our quest ends with the strong recommendation to omit early-PN for patients in the ICU, as this reduces need of blood glucose control and allows cellular housekeeping systems to play evolutionary selected roles in the recovery process. Once again, less is more in critical care.
Error in Supplement 1
Journal: JAMA Dermatology (2023)

Kristen Bibeau, PhD, MSPH; Khaled Ezzedine, MD, PhD; John E. Harris, MD, PhD; Nanja van Geel, MD, PhD; Pearl Grimes, MD; Davinder Parsad, MD; Mukta Tulpule, MBBS; Jackie Gardner, BA; Yan Valle, MSc, MBA; Gaone Tlhong Matewa, BBA; Christine LaFiura, BA; Anouk Lindley, MBA; Haobo Ren, PhD; Iltefat H. Hamzavi, MD
Managing Competing Risks for Surgical Patients With Complex Medical Problems—Considering Confounding
Authors: Laura A. Graham, Mary T. Hawn
Journal: JAMA Surgery (2023)

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Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer
Authors: Priyanka Sharma, Shane R. Stecklein, Rachel Yoder, Joshua M. Staley, Kelsey Schwensen, Anne O’Dea, Lauren Nye, Deepti Satelli, Gregory Crane, Rashna Madan, Maura F. O’Neil, Jamie Wagner, Kelsey E. Larson, Christa Balanoff, Lyndsey Kilgore, Milind A. Phadnis, Andrew K. Godwin, Roberto Salgado, Qamar J. Khan, Joyce O’Shaughnessy
Journal: JAMA Oncology (2023)

Addition of pembrolizumab to anthracycline-based chemotherapy improves pathologic complete response (pCR) and event-free survival (EFS) in triple-negative breast cancer (TNBC). The efficacy of anthracycline-free chemoimmunotherapy in TNBC has not been assessed.
Rituximab and Omalizumab Combination Therapy for Bullous Pemphigoid
Authors: Stephanie T. Le, Samantha Herbert, Reneé Haughton, Jordan Nava, Atrin Toussi, Antonio Ji-Xu, Emanual Maverakis
Journal: JAMA Dermatology (2023)

This research letter reports on a case series of 10 patients with bullous pemphigoid treated with rituximab combined with omalizumab.